Gastrointestinal cancer represent one of the major reasons for tumor related death in the United States. Current treatment options are limited to surgery, chemotherapy, radiation therapy and molecular targeted therapy and new treatment options are urgently needed. We have currently two clinical trials open for patients with advanced hepatocellular carcinoma. In these trials we evaluate the efficacy of a vascular targeting agent, Trc105. Trc 105 is a monoclonal antibody which binds to CD105 (endoglin), which is highly expressed on tumor infiltrating endothelial cells. In another trial, we are testing the drug combination of cetuximab and AZD6244, a MEK inhibitor. This trial is conducted in collaboration with a site at the University of Wisconsin. Finally we plan to open a trial in which we test an immune based approach in patients with advanced pancreatic cancer, who have failed standard chemotherapy. In this multicenter trial patients will be treated with a combination of GVAX (a GM-CSF expressing allogeneic cell line) and Listeria monocytogenes expressing mesothelin. Fianlly we are in the process of opening another study using an antibody against a target in pancreatic cancer cells as a 2nd line treatment as well as an anti-sense molecule against iEF4A in combination with irinotecan in patients with colon cancer..